{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:46:06Z","timestamp":1790682366087,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,12,30]],"date-time":"2013-12-30T00:00:00Z","timestamp":1388361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We previously showed that Cyr61 acts to promote fibroblast\u2010like synoviocyte (FLS) proliferation and Th17 cell differentiation, suggesting that Cyr61 plays an important role in mediating the joint inflammation and damage in rheumatoid arthritis (RA). The aim of this study was to investigate whether Cyr61 expression is regulated at the posttranscription level, and if so, how this regulation connects to other etiologic factors in RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Expression of microRNA\u201022 (miR\u201022) in synovial tissue was detected by real\u2010time polymerase chain reaction (PCR) using miRNA\u2010specific TaqMan MGB probes. MicroRNA\u201022 promoter activity was analyzed using a Dual\u2010Luciferase Reporter Assay. Cytokine expression was measured by enzyme\u2010linked immunosorbent assay, and the expression of other factors was measured by real\u2010time PCR or Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MicroRNA\u201022 directly targeted the 3\u2032\u2010untranslated region of <jats:italic>Cyr61<\/jats:italic> messenger RNA and inhibited Cyr61 expression. Expression of miR\u201022 was down\u2010regulated and was negatively correlated with Cyr61 expression in RA synovial tissue. Furthermore, wild\u2010type p53 activated miR\u201022 transcription by binding to the promoter region of the miR\u201022 gene, while the mutant forms of p53 frequently found in RA synovial tissue were shown to have lost the ability to activate miR\u201022 expression. As a result, miR\u201022 was down\u2010regulated, contributing to the overexpression of Cyr61 in RA FLS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results not only reveal a novel mechanism whereby p53 is involved in the posttranscriptional regulation of Cyr61 expression via miRNA\u201022, but also provide a molecular explanation for the role of somatic mutations of p53, which are frequently observed in RA synovial tissue, in the etiology of this autoimmune disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38142","type":"journal-article","created":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T16:49:00Z","timestamp":1377622140000},"page":"49-59","source":"Crossref","is-referenced-by-count":112,"title":["A Novel p53\/microRNA\u201022\/Cyr61 Axis in Synovial Cells Regulates Inflammation in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"66","author":[{"given":"Jinpiao","family":"Lin","sequence":"first","affiliation":[{"name":"Shanghai Jiao 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